One crucial step in sexual development of a child is probably the alteration in sensitivity to feedback of reproductive hormones. A number of human diseases involve malfunctions of the control of development of reproductive functions. The project involves a study of possible changes in metabolism of steroids by brain under conditions where these same steroids inhibit centers which stimulate pituitary trophic hormone secretion. It is proposed that metabolism of steroids by brain may be related to their mechanism of action on the brain centers. During the period of alteration in sensitivity to feedback during sexual development, changes in the relative rate of intracellular conversion of circulating forms of steroid hormones to other steroids of differing biological activity may be anticipated from a current hypothesis of hormone action. The aims of this work are to study the conversion of steroids such as testosterone and progesterone when they are incubated with different areas of rat brain, with particular attention being paid to quantitating changes in the relative rate of formation of different metabolites during processes such as puberty and reproductive cycles. The effects will be studied. Radioactively labeled steroids will be incubated with minces and homogenates of brain tissue. Products formed will be extracted, identified, and quantitated. Alterations in the pattern of metabolism will be looked for during changes in physiological state.